Haematological Malignancy

Question 1

1. which cells are malignant in Malignant Myeloma?
2. What is the biomarker of this malignancy?
   a) in the serum
   b) in the urine

Answer 1

1. BONE MARROW PLASMA CELLS
2. para protein
3. bence jones protein (urinary excretion of light chains)

Question 2

1. what is the mean age of presentation of malignant myeloma?
2. in which groups is malignant myeloma more common?

Answer 2

1. 60+

2. males and those of african descent

Question 3

Describe the clinical features (and the pathophysiology as to why they happen) of malignant myeloma (4)

Answer 3

1. BONE PAIN, PATHOLOGICAL FRACTURES, SPINAL CORD COMPRESSION, HYPERCALCAEMIA
   - bone lesions with increased osteoclast activity results in bone destruction
2. PANCYTOPENIA (infection, anaemia, bleeding) - due to bone marrow infiltration of plasma cells
   - thrombocytopenia + paraprotein = hyperviscosity
3. KIDNEY INJURY
   - deposition of light chains in renal tubiles
   - hypercalcaemia
   - hyperuricaemia (high cell turnover)
   - use of NSAIDs with pain
4. RECURRENT INFECTION
   - neutropenia
   - reduction in normal Ig levels

Question 4

Name 4 life threatening complications of malignant myeloma (and how they are managed)

Answer 4

1. renal impairment (may require renal replacement therapy)
2. hypercalcaemia (rehydration and bisphosphonates)
3. malignant spinal cord compression (radiotherapy within 24 hrs and dexamethasone)
4. hyperviscosity (corrected with plasmapheresis)

Question 5

What investigations should you perform for ?malignant myeloma?

Answer 5

1. FBC (Hb, WCC, platelets normal or low)
2. ESR (often raised)
3. blood film
4. U&E (may demonstrate evidence of kidney injury)
5. Serum Ca
6. serum protein electrophoresis - presence of paraprotein
7. urine electrophoresis - presence of bence jones protein
8. bone marrow aspirate and biopsy - definitive test for MM
9. whole body MRI

Question 6

What is MGUS?

Answer 6

monoclonal gammopathy of unknown significance:
- isolated serum paraprotein that does meet diagnostic criteria for symptomatic or asymptomatic myeloma.
20-30% will progress to multiple myeloma in a 25 yr period

Question 7

Describe the specific therapy for malifnant myeloma

Answer 7

1. alkylating agent - cylophosphamide or melphalan
2. steroid (pred or dex)
3. novel agent - bortezomib or thalidomide

Question 8

1. Why are cancers arising from less mature cells more aggressive?
2. Why are cancers arising from more mature cells less aggressive?

Answer 8

1. the main role of these cells is to divide - more likely to cause an acute cancer
2. the proliferative capacity of these cells is diminished as they have differentiated. More likely to cause chronic cancer

Question 9

What do the following terms usually mean:

1. leukaemia
2. -oma

Answer 9

1. presence of abnormal cells in the peripheral blood

2. solid mass. No abnormal cells in the peripheral blood

Question 10

What is the classical presentation of leukaemia related to?

Answer 10

PANCYTOPENIA secondary to bone marrow failure

• anaemia - reduction in RBC
• recurrent infection - reduction in WBCs
• bleeding - reduction in platelets

Question 11

Why do acute malignancies demonstrate a quicker/more effective response to cytotoxic agents?

Answer 11

as the malignant cells are rapidly dividing

Question 12

1. Why cant a bone marrow autograft be performed for acute malignancies?
2. How is a bone marrow autograft performed?
3. Why must a patient have a good performance status for a bone marrow transplant?

Answer 12

1. involves replacing bone marrow with early progenitors; in acute malignancies, it is these early progenitors that are malignant
2. conditioning chemo and growth factors are given; this stresses the bone marrow which produces more cells as a response; early progenitors spill over into peripheral blood, thus can be harvested
   total body irradiation to kill bone marrow prior to transplant
3. total body radiation is a radical treatment

Question 13

1. What are B symptoms caused by?
2. Give examples of B symptoms
3. Which drug can be useful in managing debilitating B symptoms?

Answer 13

1. acute inflammatory response against malignancy
2. fever, night sweats, weight loss
3. Thalidomide

Question 14

1. Which leukaemia is more common in childhood?

2. Which leukaemia is a disease of the elderly?

Answer 14

1. ALL

2. CLL

Question 15

Name 4 risk factors associated with the development of leukaemia

Answer 15

1. radiation exposure
2. chemicals and drugs - benzene, alkylating agents, topoisomerase inhibitors
3. genetic factors
4. viral infection

Question 16

What are the consequences of high WCC in acute leukaemias?

Answer 16

Leukostasis - accumulation of WBC aggregates in blood vessels which impede blood flow

Question 17

What are the consequences of substance release from leukaemic cells?

Answer 17

• disseminated intravascular coagulation

- hyperuricaemia

Question 18

What is the name given to the immature myeloid/lymphoid precursors in acute leukaemia?

Answer 18

Blast cells (myeloblasts or lymphoblasts)

Question 19

1. Which investigations are useful in a patient with ?acute leukaemia?
2. Which tests are useful in planning therapy for a patient with leukaemia?

Answer 19

1. blood count - pancytopenia
    blood film - presence of blast cells
    bone marrow aspirate
    CXR - mediastinal widening
    CSF examination
    coagulation profile (to exclude presence of disseminated intravascular coagulation)

2. U&E, LFT, serum urate
   cardiac function
   HLA type

Question 20

Describe the chemotherapy regime for ALL

1. Remission induction
2. Consolidation
3. CNS prophylaxis
4. Maintenance

Answer 20

1. vincristine, prednisolone, L-asparaginase and daunorubicin
2. daunorubicin
3. methotrexate ± CNS irradiation
4. mercaptopurine, methotrexate, vincristine and prednisolone for 2 years

Question 21

1. What type of bone marrow transplant can be given for acute leukaemia?
2. How is this performed?
3. Name 4 complications of bone marrow transplant

Answer 21

1. allograft
2. Pluripotent haematopoietic stem cells are collected from bone marrow and HLA matched to donors on database
   Chemotherapy + whole body radiation is performed to destroy leukaemic cells (+ rest of bone marrow) and then bone marrow is repopulated with infused donor cells
3. opportunistic infection, relapse of leukaemia, infertility, graft v host disease

Question 22

1. What is the genetic hallmark of CML?
2. what is the timecourse of CML?
3. What can CML progress to if not initially cured?

Answer 22

1. Philadelphia chromosome - BCR-ABL fusion protein
2. slow, progressive course
3. blast crisis (transformation to acute leukaemia)
   myelofibrosis

Question 23

Name some symptoms associated with CML

Answer 23

1. symptomatic anaemia
   abdominal discomfort attributed to splenomegaly
   weight loss
   fever and night sweats
   headache
   bleeding and bruising

Question 24

How is CML managed?

Answer 24

Imatinib!

Question 25

1. What does CLL result from? | 2. How does the disease present?

Answer 25

1. clonal expansion of small B lymphocytes which are functionally incompetent 2. majority of patients are asymptomatic and disease is detected incidentally - some patients present with features of marrow failure

Question 26

1. What is the finding of bone marrow aspiration in CLL? 2. What staging is used for CLL? 3. How is CLL managed?

Answer 26

1. heavily infiltrated with lymphocytes 2. Rai and Binet Staging 3. often managed with watchful waiting. Patients treated if they develop symptoms

Question 27

How do patients with lymphoma commonly present?

Answer 27

- peripheral lymphadenopathy - B symptoms - weight loss - fever - sweats

Question 28

1. Which diagnostic test is used to confirm diagnosis of lymphoma? 2. Which other tests are useful in the investigation of lymphoma? 3. Which tests are used to plan specific therapy?

Answer 28

1. excision biopsy of relevant tissue with histological, immunological and molecular analysis 2. - CXR to examine for mediastinal widening - CT TAP and PET for staging - bone marrow biopsy (for stage III/IV disease/HIV+ patients/patients with B symptoms) ``` 3. U&E, LFTs serum uric acid (risk of tumour lysis syndrome) virology (HIV, Hep B and C) Cardiac function Respiratory function Fertility ```

Question 29

1. What is the gender predominance of hodgkin's lymphoma? | 2. At what age is the incidence of hodgkin's lymphoma highest?

Answer 29

1. more common in males | 2. third decade of life

Question 30

Name 2 infections which increase risk of Hodgkin's Lymphoma

Answer 30

1. EBV | 2. Infectious mononucleosis

Question 31

What histology is characteristic of: 1. Classical Hodgkin's Lymphoma? 2. Non-classical Hodgkin's Lymphoma?

Answer 31

1. REED STERNBERG CELL | 2. Popcorn cell (variant of Reed Sternberg)

Question 32

Describe clinical features of Hodgkin's Lymphoma

Answer 32

- painless lymphadenopathy (usually cervical) - cough (due to disease of the mediastinum) - hepatosplenomegaly - B symptoms

Question 33

Describe the Ann Arbor Staging used in Hodgkin's Lymphoma

Answer 33

1. involvement of SINGLE lymph node/lymphoid structure/extranodal site 2. involvement of ≥2 lymph nodes or involvement of only one extranodal organ and lymph node region ON THE SAME SIDE OF THE DIAPHRAGM 3. involvement of lymph node regions on BOTH SIDES OF THE DIAPHRAGM or localised involvement of only one extranodal site 4. diffuse or disseminated involvement of ≥1 extra nodal organs/tissues with or without associated lymph node involvement

Question 34

Name the 4 unfavourable prognostic factors associated with Hodgkin's Lymphoma

Answer 34

1. 3+ sites of disease 2. bulky mediastinal disease 3. elevated ESR 4. extranodal extension

Question 35

How is Hodgkin's Lymphoma managed?

Answer 35

ABVD chemotherapy + involved field irradiation - Doxorubicin - Bleomycin - Vinblastine - Decarbazine

Question 36

Which types of Non-Hodgkin's lymphoma are more common?

Answer 36

B cell NHLs

Question 37

Name 4 risk factors associated with the development of Non-Hodgkin's Lymphoma

Answer 37

1. family hx 2. Infection - Human T cell leukaemia virus - H pylori (extra nodal lymphoma of the stomach) - chlamydia (MALT lymphoma) - EBV (Burkitt's Lymphoma) 3. inherited syndromes 4. immunosuppression

Question 38

1. Describe the pathogenesis which leads to the different subtypes of Non Hodgkin's lymphoma? 2. How are Non Hodgkin's Lymphomas classified?

Answer 38

1. malignant clonal expansion of lymphocytes occurring at different stages of lymphocyte development 2. based on their cell of origin and the stage of lymphocytic maturation at which they develop?

Question 39

1. Which NHL is the most common adult lymphoma worldwide and second most common lymphoma in childhood? 2. Which NHL is the second most common NHL? 3. Which NHL is the most common childhood malignancy worldwide?

Answer 39

1. Diffuse Large B lymphoma 2. Follicular lymphoma 3. Burkitt's Lymphoma

Question 40

Name 3 types of B cell NHLs which are aggressive

Answer 40

1. Diffuse Large B cell lymphoma 2. Follicular Lymphoma 3. Bukitt's Lymphoma

Question 41

Name the 3 types of Burkitt's Lymphoma

Answer 41

1. Endemic - associated with EBV 2. Sporadic (30% are EBV related) 3. AIDS related

Question 42

How are B cell NHLs treated?

Answer 42

R-CHOP - Rituximab - cyclophosphamide - doxorubicin - vincristine - prednisolone

Question 43

1. What is the MOA of rituximab? | 2. Why is it only used to treat B cell NHLs and not T cell?

Answer 43

1. Monoclonal antibody which targets CD-20 expressed on almost all B cell lymphomas 2. CD20 is not expressed on T cells